20 November 1965 Periodic Haemodialysis-Konotey-Ahulu et al. BRITISH 1215

Gonzales, F. M., Pabico, R. C., Brown, H. W., Maher, J. F., andSchreiner, G. E. (1963). Trans. Amer. Soc. artif. intern. Organs, 9,11.

Hegstrom, R. M., Murray, J. S., Pendras, J. P., Burnell, J. M., andScribner, B. H. (1961). Ibid., 7, 136.Murray, J. S., Pendras, J. P., Burnell, J. M., and Scribner, B. H.

(1962). Ibid., 8, 266.Lindholm, D. D., Burnell, J. M., and Murray, J. S. (1963). Ibid., 9,

3.Locke, S., Merrill, J. P., and Tyler, H. R. (1961). Arch. intern. Med.,

108, 519.Murray, J. S. Pendras, J. P., Lindholm, D. D., and Erickson, R. V.

(1964). Trans. Amer. Soc. artif. intern. Organs, 10, 191.

Osler, W. (1892). The Principles and Practice of Medicine, p. 737.Apoleton, New York.

PreswicK, G., and Jeremy, D. (1964). Lancet, 2, 731.Shaldon, S. (1963). West European Symposia on Clinical Chemistry:

"Water and Electrolyte Metabolism," II, p. 241. Amsterdam.(1965). Scientific Basis of Medicine, Annual Review. In press.Rosen, S. M., and Silva, H. (1963). West European Symposia on

Clinical Chemistry: " Water and Electrolyte Metabolism," II, p. 288.Amsterdam.

Thomas, P. K., Sears, T. A., and Gillihtt, R. W. (1959). 7. Neurol.Neurosurg. Psychiat., 22, 175.

Versaci, A. A., Olsen, K. J., McMain, P. B., Nakamoto, S., and Kolff,W. J. (1964). Trans. Amer. Soc. artif. intern. Organs, 10, 328.

Plasma Renin Concentration in Human HypertensionII: Renin in Relation to Aetiology

J. J. BROWN,* M.B., B.S., B.SC., M.R.C.P.; D. L. DAVIES,* M.B., B.S.;

A. F. LEVER,* M.B., B.S., B.SC., M.R.C.P.; J. I. S. ROBERTSON,* M.B., B.S., B.SC., M.R.C.P.

Brit. med. J., 1965, 2, 1215-1219

In previous papers (Brown et al., 1965a, 1965b) we havedemonstrated, in clinical hypertension, a close inverserelationship between renin concentration and plasma sodiumwhich appears to be independent of aetiology, the height ofthe arterial pressure, complications, and treatment. The presentcommunication is concerned with an analysis of renin andsodium in hypertension in relation to aetiology. The methodsused in this study are as given previously (Brown et al., 1965b,1965d); data on additional cases have been included, but theseries is basically that described earlier. Plasma renin concen-trations in a total of 276 hypertensive patients have been com-pared with those in 125 normal subjects having a mean reninconcentration of 8.2; S.D. 2.7 units/I. (Brown et al., 1964d).

Overactivity of the Adrenal Cortex

Primary Aldosteronism due to Adrenal Tumour

In this condition hypertension is caused by an aldosterone-secreting adrenal cortical adenoma (Conn, 1955; Mader andIseri, 1955 ; Milne et al., 1957; Conn et al., 1964b). Plasmasodium and total exchangeable sodium are often raised, whilepotassium is low. Whether all the features of the syndromecan be attributed solely to the excess aldosterone, or whetherother hormones produced by the tumour are necessary, has beenthe subject of discussion (see Ross and Hurst, 1965).The hypertension and increased exchangeable sodium are

accompained by depression of plasma renin concentration ; afterremoval of the tumour, with correction of the hypertension andelectrolyte abnormalities, renin rises into the normal range(Brown et al., 1963b, 1964a-c, 1965d) (Fig. 1).

Alternatively, the administration of spironolactone to patientswith this syndrome may correct the hypertension and electro-lytes without affecting aldosterone secretion (Brown et al.,1963b, 1964a, 1964b, 1964c, 1965d); plasma renin concentra-tion rises to normal as the sodium falls, emphasizing the inter-relationship between renin and sodium, and showing that theeffect of the adrenal overactivity on renin concentration is nota direct one but is mediated by the electrolyte abnormalities(Brown et al., 1963b, 1964a, 1964c).

Estimations of other components of the renin-angiotensinsystem have been handicapped by relative insensitivity, but in

several cases have given results in general agreement with thesemeasurements of renin concentration. Thus circulating angio-tensin has usually, thoughnot invariably, been un- BEFORE AFTER'. ~~~~OPERATION OPERATIONdetectable in primary aldo- 15steronism (Biron et al.,1962; Morris et al., 1964).Measurements of " renin 010

activity "' have been less*_consistent. Thus Yoshinaga 'et al. (1963), who used a zmodification of the method Z S /of Helmer and JudsonA(1963), reported high nor-mal levels in this disease. OKirkendall et al. (1964),' FIG. 1.-Plasma renn concentrationswith a basically similar before operation in four patients fromtechnique, found plasma whom aldosterone-producing tumours

. .activity variou were later removed. Post-operationrenin activity" variously values also shown in two. Normallow or undetectable before mean ± 1 and 2 S.D. indicated.operation in a patient withprimary aldosteronism, the values rising after removal of thetumour. Findings similar to those of Kirkendall et al. (1964),but with an occasional result well in the measurable range beforeoperation, were later published by Conn et al. (1964a), whoused the extraction procedure of Boucher et al. (1964).

Thus, while these tests may sometimes add support to the pre-operative diagnosis of primary aldosteronism, the limits of theirreliability are uncertain. In the patients we have studied reninconcentration and plasma sodium have appeared closely linked.Sodium values are not given in the case reports of Biron et al.(1962), Yoshinaga et al. (1963), Conn et al. (1964a), Kirkendallet al. (1964), and Morris et al. (1964), and it therefore remainsuncertain whether estimations of renin concentration, reninactivity, or angiotensin are capable of providing diagnosticinformation which cannot be inferred from repeated andaccurate measurement of plasma and exchangeable sodium.Leutscher (1964) refers to cases of primary aldosteronism withpersistently normal sodium, but we have not so far encounteredone. Renin measurements in such patients would be ofconsiderable theoretical and practical interest.

* Medical Unit, St. Mary's Hospital, London.1The meaning of this term has been discussed previously (Brown Et at.,

1965b).

1216 20 November 1965 Hypertension-Brown et al.

Cushing's Syndrome

The distinctive clinical features of this condition are theresult of excessive production of glucocorticoids (see Paschkiset al., 1958). In some cases, as in primary aldosteronism,hypertension may be associated with hypokalaemia and hyper-natraemia. The possible mechanisms by which steroid excessproduces the electrolyte abnormalities in the two conditions are

discussed by Mills et al. (1960), Bartter and Fourman (1962),Gwinup et al. (1964), Bagshawe et al. (1965), Gantt (1965),Ross (1965), Ross and Hurst (1965), Tashima (1965). Mooreet al. (1954), while emphasizing the difficulty of assessing totalexchangeable sodium and potassium (NaE and KE) in condi-tions where body weight is altered, found NaE (in mEq/kg.)and serum sodium normal in a case of Cushing's syndromewith hypertension. Similarly, Arons et al. (1958) found NaEnormal and KE low in four of five cases; NaE was raised inonly one of the five. Renin measurements are thus of consider-able theoretical interest in this disease.

So far we have measured renin concentration in four cases

of Cushing's syndrome with hypertension. All had clinicalstigmata of the disease, together with raised plasma cortisoland/or increased cortisol secretion rate and/or increased urinary17-hydroxycorticosteroids. Blood-pressures varied from 200/130 to 148/100 mm. Hg. The plasma renin concentrationsfound in these patients are shown in Fig. 2.

-

z

Z 5-

_- 2 S.D.

S. D.

* NORMALMEAN

*0

_ S.D.

111c 2 S.D.

FIG. 2.-Plasma renin concentrationsin four cases of Cushing's syndromewith hypertension. Normal mean ± 1

and 2 S.D. indicated.

The lowest plasma renin (3 units/l.) was found in the case

with the highest plasma sodium (145 mEq/l.). The highestplasma renin (9 units/l.) was close to the normal mean of 8.2units/l. This patient had a normal NaE (39.0 mEq/kg.), lowKE (30.2 mEq/kg.), plasma Na 143 mEq/l., and plasma K 2.2mEq/l. In the two remaining patients, both of whom hadrenin concentrations of 7 units/l., plasma electrolytes were notstrikingly abnormal (Na respectively 143 and 139; K 3.8 and4.5 mEq/l.).Although these observations permit only limited interpreta-

tion, they are not discordant with the theme of inverse relation-ship between plasma renin concentration and plasma sodium.

" Essential " Hypertension

Of 123 untreated patients with diastolic pressures of 100 mm.Hg or more only 11 could be strictly described under thisheading. None of these had retinal haemorrhages or exudatesattributable to the hypertension; none had proteinuria or

urinary infection; and none had a renal abnormality revealedby intravenous pyelography. Renal arteriography was per-formed in four, and was normal. None had evidence of aorticcoarctation or adrenal pathology, and all had a blood urea below40 mg./100 ml., plasma potassium between 3.9 and 5.2 mEq/l.,and a plasma sodium between 135 and 144 mEq/l.The mean plasma renin concentration in this group (10.0

S.E. 1.5 units/l.) did not differ significantly from the normalmean of 8.2 units/l. (t= 1.07; P>0.1).

The first column of Fig. 3 shows the relation betweenplasma renin concentration, sodium, and potassium in these 11patients with "essential" hypertension. The remaining threecolumns show the relation between renin and plasma sodiumin hypertensive patients without retinal lesions when pro-gressively lower categories of plasma potassium are considered.These groups include increasing numbers of patients withprimary aldosteronism and Cushing's syndrome, and it can beseen that plasma renin falls and plasma sodium rises in thegroups with lower potassium levels. It is possible that similarabnormalities could result from lesions other than primarytumour or hyperplasia of the adrenal cortex (Brown et al.,1964a, 1965d).

z

z

n

0~

-i

0-

10-

5 -

RENIN

NaO4

-148 r-

('I

-145>0

3

- 140-

K+ K+ K + K+3-9- 5 2 3-55-3-85 3 0-3 5 <3-0

FIG. 3.-Hypertension without retinopathy. Shows rise in sodium andfall in renin as groups with progressively lower plasma potassium areconsidered. The first column comprises the 11 cases considered to have" essential" hypertension (see text). Mean values and S.E. of mean

shown for renin and plasma sodium.

Coarctation of the Aorta

Plasma renin concentrations in four cases of hypertensionwith coarctation of the aorta were in the normal range (Fig. 4).A further estimation made in one of these patients four monthsafter surgical correction of the lesion, with consequent reduc-tion of the arterial pressure, showed no marked change in reninconcentration (Fig. 4). The number of patients studied was

too small to reveal any slight but systematic difference in plasmarenin which might exist in coarctation as a group, comparedwith normal. It is notable that Morris et al. (1964) foundarterial angiotensin higher in coarctation than in " essential"hypertension.

>50

50

_ 40-

z 30zw

20

*a.~~~~~~~~~~~~~S* ~~* T;10-

0 +*

PH^*' INTRINSICCOARCTATION ^' RENALDISEASES

FIG. 4. Plasma renin concentrations in (a) four patients with coarctationof aorta ; (b) four patients with phaeochromocytoma ; and (c) 41 patientswith various diseases of the renal parenchyma. Normal mean ± I and

2 S.D. indicated.

BRrTSHMEDICAL JOURNAL

0

.

Phaeochromocytoma

Plasma renin concentrations in four patients with hyper-tension due to adrenal medullary tumours were in the normalrange (Fig. 4). All of these patients had an increased urinaryexcretion of catecholamines. The highest renin was in the onlycase in which retinal haemorrhages and exudates were present.Again the group was too small to show whether or not reninconcentration differs systematically from normal in this condi-tion, but if any such difference exists it appears to be slight.

Renal Artery Stenosis

The minimum requirements for this diagnosis for the present

purposes were the arteriographic demonstration of a renalartery lesion, together with a persistently lower urine flow andincreased urinary creatinine (or inulin) concentration on thesuspect side on ureteric catheterization. The presence of a

stenosis by these criteria does not, of course, imply that therenal artery narrowing was necessarily the cause of the hyper-tension.

Fig. 5 shows the plasma renin concentration in 44 untreatedcases of renal artery stenosis. Nineteen had no retinal lesions.In most of these renin was in the normal range, though themean value (12.7; S.E. 1.5 units/l.) was significantly higherthan the normal mean (t=5.1; P<0.001). The distributionof renin concentration in these patients without retinopathywas similar to that found in rabbits with experimentalrenal artery stenosis and hypertension (Lever and Robertson,1964).The 25 cases with renal artery stenosis and retinopathy

(bilateral retinal haemorrhages and exudates and/or papill-oedema) were in marked contrast, plasma renin concentrationranging from the upper limit of normal to values a hundredtimes higher (highest, 1,920 units/l.). There was a significantinverse relation between plasma sodium and renin concentrationboth in the patients with and in those without retinopathy(respectively r= -0.89 and -0.63; P<0.001 and <0.01).

Plasma sodium concentration was significantly lower in the

patients with renal artery stenosis and retinopathy than in thosewithout renal lesions (respective means, 135.3 and 140.8 mEq/l.;P<0.005). Several of the former group were examples of the

hyponatraemic syndrome of severe hypertension, and have beendiscussed in more detail previously (Brown et al., 1965b). A

50

c

zz

w

x 20-

10

RETINOPATHY00

*:

NORETINOPATHY

.

0*

0

0

S.D.

S. D. +-

NORMAL

MEAN

2 S.D.

0e*0

0

0

0

I*004%0@@6

0 JRG. 5.-Plasma renin concentration in renal artery stenosis. (" Retino-pathy"=bilateral haemorrhages and exudates and/or papilloedema).

Normal mean ± 1 and 2 S.D. indicated.

BRrrISHMEDICAL JOURNAL 1217

raised aldosterone secretion rate was found in a number ofthese (see also Barraclough et al., 1965).The unusual combination of renal artery stenosis, hypo-

kalaemia, and increased aldosterone secretion, with raised plasmasodium and low plasma renin concentration was seen in one

patient previously reported (Brown et al., 1963b, 1964b, 1964c),who was found to have a renin concentration of 6.5 units/Lin peripheral plasma taken at operation for the correction ofrenal artery stenosis. After operation the hypertension, excess

aldosterone secretion, hypernatraemia, and hypokalaemia per-sisted, and plasma renin was abnormally low. This conformsclosely to the pattern seen in primary aldosteronism, and, as

we suggested earlier (Brown et al., 1963b, 1964b), thepatient probably has either an adrenal tumour which was notdiscovered at operation, or autonomous adrenal overactivity inthe absence of a tumour (see van Buchem et al., 1956 ; Bartterand Biglieri, 1958 ; Relman, 1963). (This case is not includedin Fig. 5.) The possible causal relationship between renal or

renal artery lesions and adrenal cortical autonomy in this andother instances has been discussed previously (Stanbury et al.,1958; Gowenlock and Wrong, 1962; Wrong 1963, 1964;Conn, 1964a, 1964b; Cope, 1964 ; Laragh, 1964; Brown et al.,1963b, 1964b, 1964c, 1965c, 1965e). The concept is an

interesting one, but conclusive evidence for or against iswanting.The plasma renin concentrations found in the patients with

renal artery stenosis were compared with the severity of stenosisas shown by ureteric catheterization studies.

In seven cases no urine was obtained from the affected kidneyon ureteric catheterization, four of these being found at sub-sequent operation to have thrombosed renal arteries. All sevenhad severe retinopathy, and their plasma renin concentrationsincluded six of the highest in the whole series (respectively 24,72, 82, 83, 95, 146, and 1,920 units/l.). In the remainingcases the ratio between urinary inulin (or creatinine) concen-

tration from the post-stenotic and normal kidneys was takenas a measure of the severity of the stenosis. Excluding twopatients with renal artery branch constrictions, the ratio hada mean value of 1.9 (range 1.1 to 4.0) in the group withoutretinal lesions, compared with a mean of 2.5 (range 1.1 to 6.6)in those with retinal lesions. Thus, although there was an

appreciable overlap between the groups, those with severe

retinopathy and high renin had generally the more severe renalartery stenosis.

In summary, division of the cases with renal artery stenosisinto two groups on the basis of the presence or absence ofsevere retinopathy split them also into two almost distinctranges of plasma renin concentration (Fig. 5). Together thesecases provided a continuous distribution of renin concentrationfrom the lower part of the normal range to levels a hundredtimes normal. The rise in renin values along this series was

closely followed by a progressive fall in plasma sodium, and,rather less closely, by increasing severity of renal artery stenosis.

Patients with Radiological Evidence of FibromuscularHyperplasia

Fourteen patients had the appearances of fibromuscularhyperplasia on renal arteriography (see Bernatz et al.; 1962;Sutton et al., 1963). All except one were female. Renal artery

stenosis was confirmed by ureteric catheterization studies innine, and the histological nature of the lesion by biopsy in five.The scatter of renin concentration did not differ greatly inthis group from that in renal artery stenosis as a whole (mean17.4; S.E. 3.8 units/I.).

Hyperplasia of the Juxtaglomerular Apparatus

Hyperplasia of the juxtaglomerular cells, usually accompaniedby increased granularity, was found on renal biopsy in 12 cases.

Eleven of these had renal artery stenosis and one had Cushing's

20 November 1965 Hypertension-Brown et al.

1218 20 November 1965 Hypertension-Brown et al. BmTIsN

syndrome. Plasma renin in this group tended to be high(mean 32.9 ; S.E. 6.7 units/I.).The findings thus support the suggestion that hyperplasia

of the juxtaglomerular cells is related to increased secretion ofrenin, though it must be recognized that an elevated plasmarenin concentration could well be achieved by mechanismsother than increased secretion (see Brown et al., 1965f). In thepatient with Cushing's syndrome the renal biopsy showingjuxtaglomerular hyperplasia was performed at operation foradrenalectomS after spironolactone treatment had been given.This had been accompanied by an increase in plasma reninconcentration from 9 to 16 units/l., and clearly could havecaused the juxtaglomerular changes.

Renal Lesions other than Renal Artery Stenosis

Forty-one patients had renal lesions other than renal arterystenosis (chronic glomerulonephritis in 15 ; polycystic diseasein 4 ; hydronephrosis in 6 ; renal calculi in 2 ; urinary infectionwith cellular infiltration of the renal parenchyma in 11 _; andtuberculosis, nephrocalcinosis, and hamartomat of kidney oneinstance each). Renin concentration in these cases wasscattered over a wide range (Fig. 4). Several of the cases inthis group in which renin was found to be high were examplesof the hyponatraemic hypertensive syndrome (see Brown et al.,1965b). It is clearly possible that disease of the renalparenchyma could produce this syndrome by mechanismssimilar to those resulting from stenosis of the main renal artery.

Renin in Relation to Haemoglobin Concentrationin Renal Artery Stenosis

Polycythaemia has been found in association with a varietyof renal diseases (see Brit. med 7., 1961 ; Hillas Smith, 1963;Brandt et al., 1963). Although Cotes and Lowe (1963) did notfind a significant increase in haemoglobin concentration inpatients with renal artery stenosis, Luke et al. (1965) describeda case of renal artery stenosis with increased haemoglobinconcentration and red-cell volume in which nephrectomy curedthe hypertension and restored the haemoglobin concentrationto normal. This case had severe retinopathy, but the concen-trations of the plasma electrolytes were not reported.,

Evidence relating hyperplasia of the juxtaglomerular cellsto increased erythropoietic activity has been presented by Osnes(1958), Hirashima and Takaku (1962), Reeves et al. (1963), andMitus and Toyama (1964). Hansen (1964) found increasederythropoietic activity in the urine and in extracts of the post-stenotic kidney of rabbits with experimental renal artery con-striction. An increase in haemoglobin concentration and inred-cell volume occurred in some animals. However, Cotesand Lowe (1963) did not find an increase in circulating red-cell volume in rabbits with renal ischaemia and associatedhypertension.

In 34 untreated patients with renal artery stenosis in thepresent series the relationship between renin and haemoglobinconcentration was not statistically significant (r= 0.244 ; P>0.1).As pointed out by Cotes and Lowe (1963) and by Jones et al.(1965), however, haemoglobin concentration is not always areliable index of red-cell volume.

Renin in the Hypertensive Disease of Pregnancy

Plasma renin concentration is increased in normal pregnancy(Brown et al., 1963a). In " pre-eclamptic toxaemia " (" specifichypertensive disease of pregnancy": Pickering, 1955) we havefound renin concentration to be no higher than in normalpregnancies of similar duration, and to be rather lower in themore severely affected cases. This condition has beenexcluded from the present series, and will be analysed anddiscussed in detail separately (Brown et al., to be published).

Discussion

These results amplify the previous reports of an inverserelationship between plasma sodium and renin concentrationin hypertension (Brown et al., 1965a, 1965b). Renin has beenconsistently low in hypertension with elevated sodium, as maybe found in primary aldosteronism and in Cushing's syndrome.In Cushing's syndrome with normal plasma sodium, reninconcentration has been in the normal range, while measureswhich reduce the increased sodium in primary aldosteronismraise renin concentration to normal.Many cases of hypertension with renal artery stenosis or

parenchymal renal lesions have been found to have normalplasma renin concentration. When such renal lesions havebeen accompanied by retinal evidence of the malignant phase,however, hyponatraemia and high plasma renin concentrationshave been common. This hyponatraemic syndrome is the oneform of untreated hypertension in man in which we haveconsistently found renin concentration to be abnormally high.

These findings in clinical hypertension suggest that plasmarenin is governed by changes in sodium balance, and confirmthat the relationship is independent of the aetiology of thehypertension. As we have previously shown, however (Brownet al., 1965a, 1965b), this does not exclude other influences onplasma renin, nor does it imply that the low plasma sodium isper se the stimulus causing increased renin concentration.

SummayPlasma renin concentration has been examined in relation to

aetiology in a series of patients with hypertension.The findings are in agreement with the earlier demonstration

of an inverse relationship between plasma renin and sodiumconcentration.

Renin concentration did not differ significantly from normalin uncomplicated hypertension without determined cause.Where hypertension was accompanied by hypernatraemia,

as in Cushing's syndrome and primary aldosteronism, reninconcentration was low. Renin was normal in three cases ofCushing's syndrome with normal sodium. In primary aldo-steronism renin was increased by a variety of measures whichreduced sodium.

Plasma renin was often normal in hypertension with renaldisease or renal artery stenosis. Where these lesions wereaccompanied by severe retinopathy, however, plasma sodiumwas usually low and renin concentration high. Raised aldo-sterone secretion and hypokalaemia were found in several ofthese latter cases.

Plasma renin was normal in patients with aortic coarctationor phaeochromocytoma.

We are grateful to the numerous physicians who permitted usto study cases under their care, and especially to Professor W. S.Peart and Dr. V. Wynn. Many of the investigations were per-formed by Dr. B. J. Houghton and the staff of the routine depart-ment of chemical pathology, St. Mary's Hospital. For various steroidmeasurements and for radioisotope studies we are indebted to Drs.M. A. Barraclough, C. L. Cope, Robert Fraser, V. H. T. James,and Jill McCusker. Technical assistance was provided byMessrs. Malcolm Tree, Patrick Trust, and George Todd. Messrs.G. Evans, G. H. Jantet, M. Mee, K. Owen, A. E. Thompson, andJ. P. Williams helped with ureteric catheterization studies, and Dr.D. Sutton and his staff performed the renal arteriograms. Juxta-glomerular histology was interpreted by Dr. R. A. Parker.

For financial help we are grateful to the Medical ResearchCouncil, the British Heart Foundation, the Wellcome Trust, andPfizer Ltd.

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Observations on an Apparent Chloroquine-resistant Strain ofPlasmodium falciparum in West Africa

E. E. LASCH,* M.D.; T. L. N'GUYEN,t M.D.

Brit. med. J., 1965, 2, 1219-1222

Since their development as synthetic antimalarial drugs duringthe second world war the 4-aminoquinolines have enjoyed arole of expanding importance throughout the world and arenow regarded as the drugs of choice, both for suppression andfor therapy, in malaria (Coatney, 1963). Though resistanceof human plasmodia to pyrimethamine and proguanil has longbeen known, the recognition of 4-aminoquinoline-resistantstrains of Plasmodium falciparum is of relatively recentoccurrence. Since 1961, strains showing abnormal response tochloroquine have been reported from Colombia (Young andMoore, 1961 ; Young, 1962; Moore and Lanier, 1963; Powellet al., 1963), and Brazil (Rodrigues Da Silva et al., 1961;Box et al., 1963) in South America, and from Thailand (Younget al., 1963), Vietnam (Powell et al., 1963), Cambodia (Contacoset al., 1963), and Malaya (Montgomery and Eyles, 1963;Sandosham et al., 1963) in South-east Asia. to date, chloro-quine resistance, though suspect-. (Chemotherapy of Malaria,

* Chief Paediatric Service, Ouagadougou lospital, Ouagadougou, UpperVolta.

t Chief Bacterioiogical Service, Ouagadc ugou Hospital, Ouagadougou,Upper Volta.

1961), has not been reported from the African Continent, wherethe use of chloroquine as an antimalarial drug is widespread.

In this paper we report the results of some observationswhich, while not pretending to furnish an absolute and finalproof of resistance of P. falciparum to chloroquine, do tend tostrengthen suspicion of its existence. These observations leadus to believe that there exists in this part of West Africa (UpperVolta) a strain or several strains of P. falciparum less sensitiveto chloroquine than usually admitted.

Material and MethodsThe present report is based on a study of 15 patients from

Upper Volta, West Africa, who either developed malignanttertian malaria while taking chloroquine sulphate (Nivaquine)as a suppressive (nine cases) or failed to respond to treatmentby this drug or by chloroquine phosphate (Aralen) (six cases).The patients were children hospitalized in the paediatric

ward of the Ouagadougou Hospital. All are African children